Abstract
The role of Dickkopf-3 (Dkk3)/REIC (The Reduced Expression in Immortalized Cells), a Wnt-signaling inhibitor, in male reproductive physiology remains unknown thus far. To explore the functional details of Dkk3/REIC in the male reproductive process, we studied the Dkk3/REIC knock-out (KO) mouse model. By examining testicular sections and investigating the sperm characteristics (count, vitality and motility) and ultrastructure, we compared the reproductive features between Dkk3/REIC-KO and wild-type (WT) male mice. To further explore the underlying molecular mechanism, we performed RNA sequencing (RNA-seq) analysis of testicular tissues. Our results showed that spermiation failure existed in seminiferous tubules of Dkk3/REIC-KO mice, and sperm from Dkk3/REIC-KO mice exhibited inferior motility (44.09 ± 8.12% vs. 23.26 ± 10.02%, p < 0.01). The Ultrastructure examination revealed defects in the sperm fibrous sheath of KO mice. Although the average count of Dkk3/REIC-KO epididymal sperm was less than that of the wild-types (9.30 ± 0.69 vs. 8.27 ± 0.87, ×106), neither the gap (p > 0.05) nor the difference in the sperm vitality rate (72.83 ± 1.55% vs. 72.50 ± 0.71%, p > 0.05) were statistically significant. The RNA-seq and GO (Gene Oncology) enrichment results indicated that the differential genes were significantly enriched in the GO terms of cytoskeleton function, cAMP signaling and calcium ion binding. Collectively, our research demonstrates that Dkk3/REIC is involved in the process of spermiation, fibrous sheath integrity maintenance and sperm motility of mice.
Highlights
Infertility is a serious problem that affects over 14% of couples in the world, and half of the cases can be attributed to male factors [1]
We noticed that spermiation failure existed in Dkk3/REIC-KO mice testes, and disordered placement of differentiated spermatids was commonly found in their testicular seminiferous tubles
For the Molecular Function (MF) category, calcium ion binding and cAMPThe role of Wnt signaling in the male reproductive system has long concerned redependent protein kinase activity were the most significantly enriched Gene Ontology (GO) terms
Summary
Infertility is a serious problem that affects over 14% of couples in the world, and half of the cases can be attributed to male factors [1]. With the help of modern techniques in molecular biology, genetic disorders have been proven to be a major cause of male infertility, especially for those with non-obstruction in the genital ducts [2]. Over 2000 genes have been reported to participate in male reproductive physiology, and new findings continue emerging [3]. Wnt signaling, a classical intercellular pathway that regulates cellular proliferation and tissue development, plays a pivotal role in male reproductive function [4,5]. Among the Wnt signal community, Dickkopf (Dkk) family, a negative regulator of. Wnt signaling, has recently attracted attention from scholars in male reproduction fields.
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